HDL-Atherosclerosis Treatment Study (HATS)
Primary Purpose
Cardiovascular Diseases, Coronary Disease, Heart Diseases
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
simvastatin
niacin
antioxidants
Sponsored by
About this trial
This is an interventional prevention trial for Cardiovascular Diseases
Eligibility Criteria
Men and women with low HDL cholesterol, with at least one 50% stenotic coronary lesion or three 30% stenotic coronary lesions. Women range in age from 35 to less than 68 and men from 35 to less than 63.
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000553
First Posted
October 27, 1999
Last Updated
February 8, 2016
Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00000553
Brief Title
HDL-Atherosclerosis Treatment Study (HATS)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2005
Overall Recruitment Status
Completed
Study Start Date
September 1994 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2001 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
University of Washington
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
Brief Summary
To measure the effects of lipid-lowering drugs and/or antioxidant vitamins on progression or regression of coronary heart disease as measured by quantitative angiography in patients with low high density lipoprotein (HDL) cholesterol.
Detailed Description
BACKGROUND:
More than one-third of patients with coronary disease have "low" high density lipoprotein cholesterol (HDLc) levels (less than 35 mg/dl; United States 20th percentile) and "normal" low density lipoprotein cholesterol (LDLc) (less than 145; United States mean), a group for whom current treatment guidelines are not based on clinical trial data. Low HDLc levels are strong, independent predictors of cardiovascular disease and cardiovascular mortality risk, equally so for both men and women. This high coronary artery disease risk may be due to an imbalance between delivery of cholesterol into the arterial intima by LDL and its removal by HDL. Also, since HDL serve as antioxidants and cytoprotectants, an important HDL role may be to prevent LDL oxidation and thus limit macrophage-mediated intimal lipid accumulation or to prevent vascular cell toxicity. Recent epidemiologic, experimental, and clinical trial evidence suggests that a 15 mg/dl rise in HDL cholesterol would reduce coronary artery disease incidence and mortality by 30 to 70 percent and that antioxidant vitamins E, C, and beta-carotene might reduce coronary artery disease events and atherogenesis. The potential absolute benefit is much greater in those with existing coronary artery disease. It has also been shown that HDLc rises in response to exercise, smoking cessation, weight reduction, and monounsaturated fats.
DESIGN NARRATIVE:
Randomized, Phase III. Each patient was randomly assigned to a lipid-altering strategy or its placebo and to an antioxidant vitamin strategy or its placebo, in a 2 x 2 factorial design. The four groups were simvastatin-niacin plus an antioxidant vitamin cocktail; simvastatin-niacin plus vitamin placebo; antioxidant vitamins alone plus simvastatin-niacin placebo; or placebos for both strategies. All groups were counseled with respect to diet, exercise, and smoking cessation. The primary endpoint was the average change in proximal obstructive disease during the 2.5 year interval between baseline and the followup study. Secondary endpoints included the frequency of cardiac events, including cardiac death, confirmed non-fatal myocardial infarction, cerebrovascular accident, or revascularization by bypass or angioplasty for medically refractory unstable ischemia. The trial ended in August, 1999.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Coronary Disease, Heart Diseases, Myocardial Ischemia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Allocation
Randomized
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
simvastatin
Intervention Type
Drug
Intervention Name(s)
niacin
Intervention Type
Drug
Intervention Name(s)
antioxidants
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
68 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Men and women with low HDL cholesterol, with at least one 50% stenotic coronary lesion or three 30% stenotic coronary lesions. Women range in age from 35 to less than 68 and men from 35 to less than 63.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruce Brown
Organizational Affiliation
University of Washington
12. IPD Sharing Statement
Citations:
PubMed Identifier
7572694
Citation
Brown G, Stewart BF, Zhao XQ, Hillger LA, Poulin D, Albers JJ. What benefit can be derived from treating normocholesterolemic patients with coronary artery disease? Am J Cardiol. 1995 Sep 28;76(9):93C-97C. doi: 10.1016/s0002-9149(99)80477-9.
Results Reference
background
PubMed Identifier
9594927
Citation
Brown BG, Zhao XQ, Chait A, Frohlich J, Cheung M, Heise N, Dowdy A, DeAngelis D, Fisher LD, Albers J. Lipid altering or antioxidant vitamins for patients with coronary disease and very low HDL cholesterol? The HDL-Atherosclerosis Treatment Study Design. Can J Cardiol. 1998 Apr;14 Suppl A:6A-13A.
Results Reference
background
PubMed Identifier
9920522
Citation
Cheung MC, Wolfbauer G, Brown BG, Albers JJ. Relationship between plasma phospholipid transfer protein activity and HDL subclasses among patients with low HDL and cardiovascular disease. Atherosclerosis. 1999 Jan;142(1):201-5. doi: 10.1016/s0021-9150(98)00190-7.
Results Reference
background
PubMed Identifier
11757504
Citation
Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001 Nov 29;345(22):1583-92. doi: 10.1056/NEJMoa011090.
Results Reference
background
PubMed Identifier
12377728
Citation
Brown BG, Cheung MC, Lee AC, Zhao XQ, Chait A. Antioxidant vitamins and lipid therapy: end of a long romance? Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1535-46. doi: 10.1161/01.atv.0000034706.24149.95.
Results Reference
background
PubMed Identifier
24603218
Citation
Williams PT, Zhao XQ, Marcovina SM, Otvos JD, Brown BG, Krauss RM. Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease. Atherosclerosis. 2014 Apr;233(2):713-720. doi: 10.1016/j.atherosclerosis.2014.01.034. Epub 2014 Jan 30.
Results Reference
derived
PubMed Identifier
23460815
Citation
Williams PT, Zhao XQ, Marcovina SM, Brown BG, Krauss RM. Levels of cholesterol in small LDL particles predict atherosclerosis progression and incident CHD in the HDL-Atherosclerosis Treatment Study (HATS). PLoS One. 2013;8(2):e56782. doi: 10.1371/journal.pone.0056782. Epub 2013 Feb 27.
Results Reference
derived
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HDL-Atherosclerosis Treatment Study (HATS)
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